Oxidatlve damage in tissues of endotoxin-treated Mn-SOD transgenic mice

The toxic effect of endotoxin is partly attributable to oxidative damage resulting from increased generation of reactive oxygen species. Mn-SOD is an important antioxidant enzyme in aerobic organisms. Studies were conducted to determine if increased expression of Mn-SOD gene alters cellular susceptibility to endotoxin. Twelve-week old male B6C3 mice, engineered to express Mn-SOD in multiple organs, and their non-transgenic littermates were treated with endotoxin intraperitoneally at the dose of 20 mg/kg body weight for 24 hours. Immediately following sacrifice, liver, heart and lung were analyzed for levels of oxidation products. Relative to the controls, the levels of thiobarbituric acid reactants (TBAR) were significantly higher in the liver of endotoxin-treated mice. However, the increase of hepatic TBAR levels was significantly smaller in Mn-SOD transgenic mice than in the non-transgenic littermates. Endotoxin-treatment also resulted in significant increases in the levels of cardiac TBAR and hepatic conjugated dienes in non-transgenic mice, but not in Mn-SOD mice. Endotoxin did not significantly alter the levels of protein carbonyls in liver, lung or heart of Mn-SOD transgenic or non-transgenic mice. The results obtained suggest that increased expression of Mn-SOD gene is capable of attenuating endotoxin-induced oxidative damage in mice.